Mitchell, Tara C.

Background Sinonasal mucosal melanoma has poor survival despite multimodality treatment. While the impact of immunotherapy (IT) on metastatic cutaneous melanoma is well-defined, there are relatively little data on sinonasal mucosal melanoma. Objective We sought to define immunotherapy outcomes in patients with sinonasal mucosal melanoma. Methods A retrospective cohort study evaluated patients treated with IT during their overall treatment strategy for SNMM. Patient demographics, treatment, and survival outcomes were recorded. Results 52 patients had IT treatment for SNMM from 2000 to 2022, with an average age of 69.1 ± 11.9 years. The most common treatment was surgery with radiation and IT ( n = 26, 50%). Most regimens consisted of a combination of Nivolumab and Ipilimumab ( n = 17, 32.7%) or pembrolizumab ( n = 14, 26.9%). 44.2% of patients experienced reported complications. Overall survival at 1-, 2-, and 5 years was 86.9%, 74.1%, and 39.1%, respectively. Conclusion Approximately half of patients will have a local response following immunotherapy, but it is rare to have improvement at metastatic locations. Further research within our group will assess optimal timing and markers that are predictive of response.

Since the first approval for immune checkpoint inhibitors (ICIs) for the treatment of cutaneous melanoma more than a decade ago, immunotherapy has completely transformed the treatment landscape of this chemotherapy-resistant disease. Combination regimens including ICIs directed against programmed cell death protein 1 (PD-1) with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents or, more recently, anti-lymphocyte-activation gene 3 (LAG-3) agents, have gained regulatory approvals for the treatment of metastatic cutaneous melanoma, with long-term follow-up data suggesting the possibility of cure for some patients with advanced disease. In the resectable setting, adjuvant ICIs prolong recurrence-free survival and several are FDA-approved. Although not yet approved, neoadjuvant ICIs have also shown to improve event-free survival and remains an ongoing area of investigation. Other immunotherapy strategies, such as oncolytic virotherapy for injectable cutaneous melanoma, bispecific T-cell engager therapy for HLA-A*02:01 genotype-positive uveal melanoma, and lifileucel, an autologous tumor-infiltrating lymphocyte therapy, for unresectable or metastatic melanoma are also available to patients. Despite the remarkable efficacy of these regimens for many patients with cutaneous melanoma, traditional immunotherapy biomarkers (ie, programmed death-ligand 1 expression, tumor mutational burden, T-cell infiltrate and/or microsatellite stability) have failed to reliably predict response. Furthermore, ICIs are associated with unique toxicity profiles, particularly for the highly active combination of anti-PD-1 plus anti-CTLA-4 agents. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of melanoma, including rare subtypes of the disease (eg, uveal, mucosal), with the goal of improving patient care by providing guidance to the oncology community. Drawing from published data and clinical experience, the Expert Panel developed evidence- and consensus-based recommendations for healthcare professionals using immunotherapy to treat melanoma, with topics including therapy selection in the advanced and perioperative settings, intratumoral immunotherapy, when to use immunotherapy for patients with BRAF V600-mutated disease, management of patients with brain metastases, evaluation of treatment response, special patient populations, patient education, quality of life, and survivorship, among others.